This invention relates to novel 2-{6-[4-(2-hydroxy-ethyl)-piperazin-1-yl]-2-methyl-pyrimidin-4-ylamino}-thiazole-5-carboxylic acid (2-chloro-6-methyl-phenyl)-amide derivatives, and pharmaceutically acceptable acid addition salts thereof. The invention also provides compositions comprising a compound of this invention and the use of such compositions in methods of treating diseases and conditions beneficially treated by the inhibition of kinases including Src-kinase and Bcr-Abl kinase.
The kinase inhibitor, 2-{6-[4-(2-Hydroxy-ethyl)-piperazin-1-yl]-2-methyl-pyrimidin-4-ylamino}-thiazole-5-carboxylic acid (2-chloro-6-methyl-phenyl)-amide, is disclosed in U.S. Pat. No. 7,125,875 and U.S. Pat. No. 6,596,746, and is identified as dasatinib.
This inhibitor of Src-kinase and Bcr-Abl kinase is used to treat chronic myelogenous leukemia and Philadelphia chromosome-positive acute lymphoblastic leukemia and has been studied or is currently in 37 clinical trials (see ClincalTrials.gov website for Sprycel®). In addition to the approved indications, dasatinib is also in trials for refractory solid tumors, breast cancer, prostate cancer, myeloproliferative disorders, and chronic lymphocytic leukemia.
Dasatinib is extensively metabolized in humans, primarily by CYP 3A4. A number of these metabolites are disclosed in WO 2006/099474 and also reported for treatment of cancer, although no kinase inhibitory activity is disclosed for the compounds.
Despite the beneficial uses of dasatanib, a need remains for new and improved agents to treat cancer.